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Free keywords:
CYTOPLASMIC MESSENGER-RNA; HUMAN PM-SCL; RIBOSOMAL-RNA; YEAST EXOSOME;
CORE EXOSOME; CRYO-EM; PIGGYBAC TRANSPOSASE; DEGRADATION PATHWAY;
LIN28-LET-7 PATHWAY; MULTIPLE-MYELOMALife Sciences & Biomedicine - Other Topics;
Abstract:
The nuclear RNA exosome complex mediates the processing of structured RNAs and the decay of aberrant non-coding RNAs, an important function particularly in human cells. Most mechanistic studies to date have focused on the yeast system. Here, we reconstituted and studied the properties of a recombinant 14-subunit human nuclear exosome complex. In biochemical assays, the human exosome embeds a longer RNA channel than its yeast counterpart. The 3.8 angstrom resolution cryo-EM structure of the core complex bound to a single-stranded RNA reveals that the RNA channel path is formed by two distinct features of the hDIS3 exoribonuclease: an open conformation and a domain organization more similar to bacterial RNase II than to yeast Rrp44. The cryo-EM structure of the holo-complex shows how obligate nuclear cofactors position the hMTR4 helicase at the entrance of the core complex, suggesting a striking structural conservation from lower to higher eukaryotes.
